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Molecular Imaging and Contrast Agent Database (MICAD) [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2004-2013.

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Molecular Imaging and Contrast Agent Database (MICAD) [Internet].

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, PhD
National Center for Biotechnology Information, NLM, NIH
Corresponding author.

Created: ; Last Update: January 9, 2011.

Chemical name:99mTc-Ethylenedicysteine-folateimage 37 in the ncbi pubchem database
Abbreviated name:99mTc-EC-folate
Agent category:Compound
Target:Folate receptor
Target category:Receptor
Method of detection:Single-photon emission computed tomography (SPECT), gamma planar
Source of signal:99mTc
  • Checkbox In vitro
  • Checkbox Rodents
Click on the above structure for additional information in PubChem.



Folic acid is a water-soluble B vitamin (1). It is essential for methylation and DNA synthesis. The primary pathway for entry of folate into cells is through facilitated transporter, which has a low affinity for folate with Km of 1-5 μM. Some cells in choroid plexus, kidney, lung, thyroid, spleen, placenta, and thymus also possess a higher affinity (Kd, 0.5 nM) receptor that allows folate uptake via receptor-mediated endocytosis. Some human epithelial tumor cells were found to overexpress folate receptors (2). More than 90% of human ovarian and endometrial cancers express the high-affinity receptor, which is absent in the normal tissues. Breast, colorectal, renal, and lung carcinomas also over-expressed the folate receptor but to a lesser frequency (20-50%). 99mTc-EC-folate was synthesized and developed as a folate receptor imaging agent (3).



L, L-Ethylenedicysteine (EC) was conjugated to folate-NH2 using sulfo-N-hydroxysulfosuccinimide (3). One EC (M.W. 268 Da) residue was estimated to conjugate to folate-NH2 (M.W. 483 Da) to form EC-folate. 99mTc was complexed efficiently to EC-Folate to form 99mTc-EC-folate with a radiochemical purity of >95%. The specific activity was calculated to be about 10 μCi/μg (0.37 MBq/μg) before in vivo injection to rats.

In Vitro Studies: Testing in Cells and Tissues


99mTc-EC-folate was found to be stable at dog serum samples at 37ºC up to 4 h (3).

Animal Studies



Rats were inoculated with rat mammary tumor cells, followed by intravenous injection (10 μCi/rat, 0.37 MBq/rat, 10 μg/rat) of 99mTc-EC-folate or 99mTc-EC 14 -17 days after tumor transplantation (3). Tumor-to-blood uptake ratios for 99mTc-EC-folate rats increased as a function of time, whereas these ratios decreased for 99mTc-EC in the same period. Tumor uptake in 99mTc-EC-folate rats was about 1-fold higher than 99mTc-EC rats. The kidneys and liver were the organs with high uptakes of both tracers. Both tracers were excreted mainly in the urine. Co-injections of rats with 0.15 mol/kg of unlabeled folate blocked the uptake of 99mTc-EC-folate by 30%.

Scintigraphic images of rats given 99mTc-EC-folate (0.5 mCi/rat, 18.5 MBq/rat, 50 μg/rat) showed that tumors in the right hind legs could be well visualized at 1-4 h (3). 99mTc-EC-folate could be a useful tool for imaging folate receptor positive tumors.

Other Non-Primate Mammals


No publication is currently available.

Non-Human Primates


No publication is currently available

Human Studies


No publication is currently available.

NIH Support



Stanger O. Physiology of folic acid in health and disease. Curr Drug Metab. 2002;3(2):211–23. [PubMed: 12003352]
Ke C. Y., Mathias C. J., Green M. A. The folate receptor as a molecular target for tumor-selective radionuclide delivery. Nucl Med Biol. 2003;30(8):811–7. [PubMed: 14698784]
Ilgan S., Yang D. J., Higuchi T., Zareneyrizi F., Bayhan H., Yu D., Kim E. E., Podoloff D. A. 99mTc-ethylenedicysteine-folate: a new tumor imaging agent. Synthesis, labeling and evaluation in animals. Cancer Biother Radiopharm. 1998;13(6):427–35. [PubMed: 10851435]


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